To investigate the effect of selective hypothermia on regional cerebral blood flow (rCBF), brain tissue metabolism and neurotransmitter release in rats, we newly developed a brain thermoregulator for small animals. In the first year, regional brain temperature and rCBF were simultaneously measured using a Teflon-coated combined platinum electrode and thermocouple probe inserted into the parietal cortex and the thalamus in spontaneously hypertensive rats (SHR). In the second year, one hour of forebrain ischemia was induced by bilateral carotid artery ligation, and the concentrations of brain tissue metabolites were measured enzymatically. The difference in regional brain temperature between the cortex and the thalamus became greater when cortical temperature was set to the lower level such as 30ﾟC than 37ﾟC.In the rats induced selective brain hypothermia (30ﾟC) immediately after the initiation of ischemia, the level of adenosine triphosphate (ATP) was significantly higher than that in n
… Moreormothermic rats (36ﾟC). Our study suggests 1) the newly developed brain thermo-regulator is useful in the small animal experiments, 2) regional brain temperature regulates regional cerebral blood flow, and 3) selective brain hypothermia is effective and cytoprotective in the treatment of brain ischemia.In the final year, we examined whether brain hypothermia modulates the release of excitatory or inhibitory amino acids during cerebral ischemia in the hippocampus of aged SHR using a microdialysis technique. Hippocampal temperature was maintained 36ﾟC (normothermia), 33ﾟC (mild hypothermia) or 30ﾟC (moderate hypothermia), and rectal temperature 37ﾟC in this study. During cerebral ischemia, concentrations of glutamate, aspartate and glycine significantly increased 6-, 5-and 2-fold the resting values, respectively, in the normothermic rats, whereas hypothermia markedly inhibited the rise to 220,110 and 80% of the resting values. Similarly the elevation of taurine was 16-fold in the normothermic rats and significantly attenuated to 3-to 10-fold in both moderately and mildly hypothermic rats. The hypothermia also attenuated the ischemia-induced elevation of GABA.Histopathological grading of ischemic damage in the hippocampal CA1 areas after 7 days was significantly ameliorated in the moderate hypothermic rats (0.5 <plus-minus> 0.4) compared with the normothermic ones (1.8 <plus-minus> 0.3). These results suggest that brain hypothermia protects the neurons against ischemic insult in the hippocampus of aged SHR,and it may be, at least in part, attributed to the preservation of synaptic homeostasis preventing the excessive release of both excitatory and inhibitory amino ac36℃群では、脳虚血負荷により、Glu(グルタミン酸)、Asp(アスパラギン酸)、Gln(グリシン)はそれぞれ虚血前の6、5、2倍に増加したが、低脳温群ではほとんど上昇しなかった。またTau(タウリン)、GABAの増加も、脳温度を下げることで有意にその増加が抑制された。さらに7日後に、上記ラットの海馬CA1領域神経細胞の病理学的変化を観察したところ、30℃群では他2群に比し、明らかに神経細胞の脱落(壊死)が少なかった。以上の結果は、低脳温が脳虚血後の神経伝達物質の過剰放出と神経細胞障害を抑制し、やはり神経細胞保護作用を有することが明らかとなった。これらの基礎的研究は、将来の急性期脳血管障害の治療の一助となる可能性を秘めている。 Less